Zhao J X, Chen X H, Li J L, Pan J, Tan Y H, Xu Z F, Ren F G, Zhang Y F, Xu J, Li M Q, Li J, Zhang N, Chang J M, Wang X J, Wang H W
Department of Hematology, the Second Hospital of Shanxi Medical University, Taiyuan 030001, China.
Zhonghua Xue Ye Xue Za Zhi. 2016 Aug 14;37(8):676-81. doi: 10.3760/cma.j.issn.0253-2727.2016.08.009.
To investigate frequency and clinical features of additional sex combs-like 2 (ASXL2) gene mutation in acute myeloid leukemia (AML) patients with AML1-ETO fusion gene and to analyze the relationship between ASXL2 gene mutation and c- kit gene mutation.
Mutation analysis of exon 11 and 12 of ASXL2 gene in 59 de novo AML patients was performed by using polymerase chain reaction (PCR) followed by sequence analysis. The clinical features, survival curve and c-kit gene mutation in ASXL2 gene mutation positive and negative patients were compared.
In a total of 59 AML patients with AML1-ETO fusion gene positive, 11.9% (7/59) patients harboured ASXL2 gene mutations. The hemoglobin levels of patients with mutated ASXL2 gene [56.2 (38.0- 72.0) g/L] were significantly lower than those with wild type ASXL2 [69.0(37.2-154.0) g/L] (P=0.038). Differences were not observed in white blood cell counts, platelet counts, the proportion of acidophilic cell, and the proportion of primitive cell in the marrow between patients with mutant ASXL2 and ones without mutant ASXL2 (P>0.05). None of all 59 patients suffered from liver, spleen, central nervous system metastases in both groups. Moreover, enlarged lymph nodes was similar between patients with mutant ASXL2 and ones without mutant ASXL2 (P=0.859). Immunophenotypic analysis: in positive group CD33 positive expression was significantly lower than that of negative group (P=0.033). cCD3 was not expressed in both groups. Expression levels of CD117, cMPO, HLA-DR, CD34, CD38, CD13, CD44, CD15, CD64, CD11b, CD56, CD19, cCD79a and CD7 were similar between patients with mutant ASXL2 and ones without mutant ASXL2 (P>0.05). All of 59 patients were in remission (P=0.577). Overall survival was similar between patients with mutant ASXL2 and ones without mutant ASXL2 (P=0.631). The mutation rates of c- kit in positive group and negative group were 14.3% and 29.4%, without statistical significance (P= 0.697).
ASXL2 mutation may be a new event that can cooperate with AML1-ETO to induce leukemia. Patients in AML1- ETO positive AML with ASXL2 mutation show specific clinical characteristics of hemoglobin levels and expression level of CD33. ASXL2 gene mutations and c-kit gene mutations may not have a specific correlation between them.
探讨急性髓系白血病（AML）患者中额外性梳状样2（ASXL2）基因突变的频率及临床特征，并分析ASXL2基因突变与c-kit基因突变之间的关系。
采用聚合酶链反应（PCR）及序列分析对59例初发AML患者的ASXL2基因第11和12外显子进行突变分析。比较ASXL2基因突变阳性和阴性患者的临床特征、生存曲线及c-kit基因突变情况。
在59例AML1-ETO融合基因阳性的AML患者中，11.9%（7/59）的患者存在ASXL2基因突变。ASXL2基因突变患者的血红蛋白水平[56.2（38.0 - 72.0）g/L]显著低于野生型ASXL2患者[69.0（37.2 - 154.0）g/L]（P = 0.038）。ASXL2基因突变患者与未突变患者在白细胞计数、血小板计数、嗜酸细胞比例及骨髓原始细胞比例方面未观察到差异（P>0.05）。两组59例患者均无肝、脾、中枢神经系统转移。此外，ASXL2基因突变患者与未突变患者的淋巴结肿大情况相似（P = 0.859）。免疫表型分析：阳性组CD33阳性表达显著低于阴性组（P = 0.033）。两组均未表达cCD3。ASXL2基因突变患者与未突变患者之间CD117、cMPO、HLA-DR、CD34、CD38、CD13、CD44、CD15、CD64、CD11b、CD56、CD19、cCD79a和CD7的表达水平相似（P>0.05）。59例患者均处于缓解期（P = 0.577）。ASXL2基因突变患者与未突变患者的总生存期相似（P = 0.631）。阳性组和阴性组c-kit基因突变率分别为14.3%和29.4%，无统计学意义（P = 0.697）。
ASXL2突变可能是一种可与AML1-ETO协同诱导白血病的新事件。ASXL2突变的AML1-ETO阳性AML患者具有血红蛋白水平及CD33表达水平的特定临床特征。ASXL2基因突变与c-kit基因突变之间可能不存在特定相关性。
